Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

{"title":"[Fine-needle aspiration cytology and fine-needle aspirate calci-tonin measurement for diagnosing medullary thyroid carci-noma: a meta-analysis].","authors":"Jianhua Zhang, Junkang Yu, Chenhao Huang, Minghuang Zhang, Kanghui Zhang, Ning Meng","doi":"10.3724/zdxbyxb-2025-0401","DOIUrl":"10.3724/zdxbyxb-2025-0401","url":null,"abstract":"<p><strong>Objectives: </strong>To systematically evaluate the diagnostic value of fine-needle aspiration cytology (FNAC) and fine-needle aspirate calcitonin (FNA-CT) measurement in medullary thyroid carcinoma (MTC). This study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD420251243288) and was conducted and reported in accordance with the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) 2018.</p><p><strong>Methods: </strong>Relevant studies evaluating FNAC and FNA-CT for the diagnosis of MTC were systematically searched in Chinese and English databases from January 1, 1995 to December 31, 2024. The methodological quality of the included studies was assessed using the QUADAS-2, and meta-analysis was performed using Stata 16.0. The threshold effect was evaluated using the Spearman correlation test, and heterogeneity was assessed using Cochran's Q test and the <i>I</i>² statistic. A fixed-effects or random-effects model was selected according to the degree of heterogeneity. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated, and summary receiver operating characteristic (SROC) curves and forest plots were generated to evaluate diagnostic performance. Meta-regression analysis was further conducted to explore potential sources of heterogeneity. Deeks' funnel plot was used to assess publication bias, while Fagan nomogram and the likelihood ratio scattergram were used to evaluate clinical utility.</p><p><strong>Results: </strong>A total of 13 studies involving 937 patients with 444 MTC lesions were finally included. The Spearman correlation test showed no obvious threshold effect for FNAC in diagnosing MTC, whereas a potential threshold effect was observed for FNA-CT. Heterogeneity analysis revealed varying degrees of heterogeneity across the diagnostic performance indicators of both FNAC and FNA-CT; therefore, random-effects models were used for pooled analysis. For FNAC, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.56 (95%CI: 0.51-0.61), 0.98 (95%CI: 0.94-1.00), 34.25 (95%CI: 8.98-130.62), 0.45 (95%CI: 0.39-0.51), and 76.97 (95%CI: 18.72-316.52), respectively. For FNA-CT, the corresponding values were 0.98 (95%CI: 0.94-0.99), 0.97 (95%CI: 0.94-0.99), 37.42 (95%CI: 16.91-82.80), 0.02 (95%CI: 0.01-0.06), and 1891.55 (95%CI: 351.09-10 191.13), respectively. The SROC AUCs of FNAC and FNA-CT for diagnosing MTC were 0.65 and 1.00, respectively. Meta-regression analysis suggested that the heterogeneity of FNAC might be related to study design and detection method, whereas no significant source of heterogeneity was identified for FNA-CT. Possible publication bias was detected for both methods. Both Fagan nomogram analysis and likelihood ratio scattergram analysis showed that FNA-CT ","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"561-570"},"PeriodicalIF":0.0,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Association between blood mitochondrial DNA copy number and adverse pregnancy outcomes: a Mendelian randomization analysis].","authors":"Chunting Xiao, Zhenyin Chen, Weike Li, Rufei Gao, Zhiyi Zhou, Yuanlan Chen","doi":"10.3724/zdxbyxb-2025-0890","DOIUrl":"https://doi.org/10.3724/zdxbyxb-2025-0890","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the relationship between blood mitochondrial DNA (mtDNA) copy number and adverse pregnancy outcomes using a Mendelian randomization (MR) approach.</p><p><strong>Methods: </strong>Data were obteined from the IEU OpenGWAS project. A Mendelian randomization (MR) approach was conducted, with single nucleotide polymorphisms (SNPs) associated with blood mtDNA copy number being used as instrumental variables. Firstly, the causal relationship between blood mtDNA copy number and adverse pregnancy outcomes was evaluated through univariate MR analysis. Further conduct multivariate MR analysis and adjust lactate levels to eliminate confounding effects of lactate metabolism. Finally, conduct reverse MR analysis to explore the reverse effect of adverse pregnancy outcomes on blood mtDNA copy number. Inverse variance weighted (IVW) was used as the primary analysis method, supplemented by MR-Egger regression, weighted median, simple mode, and weighted mode. Sensitivity analyses including MR-Egger intercept test, Cochran's Q test, MR-PRESSO, and leave-one-out analysis were conducted to ensure robustness. Multivariable MR was performed to adjust for lactate levels. Reverse MR analysis was also carried out.</p><p><strong>Results: </strong>In forward univariable MR, genetically predicted blood mtDNA copy number was causally associated with gestational hypertension (OR=0.719, 95%CI: 0.538-0.961, <i>P</i> < 0.05), pregnancy complicated with chronic hypertension (OR=0.719, 95%CI: 0.538-0.961, <i>P</i> < 0.05), preeclampsia (OR=0.616, 95% CI: 0.412-0.922, <i>P</i>< 0.05), and premature rupture of membranes (OR = 1.478, 95% CI: 1.008-2.168, <i>P</i> < 0.05). Multivariable MR adjusting for lactate levels showed that these causal effects remained significant, with effect sizes comparable to univariate estimates. Reverse MR indicated that premature rupture of membranes (β = 0.009, 95% CI: 0.001-0.017, <i>P</i> < 0.05), excessive vomiting during pregnancy (β = -0.004, 95% CI: -0.007-0.000, <i>P</i> < 0.05), and early pregnancy bleeding (β=0.008, 95%CI: 0.002-0.015, <i>P</i> < 0.01) were associated with blood mtDNA copy number. Sensitivity analyses confirmed the reliability of these findings.</p><p><strong>Conclusions: </strong>Blood mtDNA copy number is causally related to gestational hypertension, chronic hypertension in pregnancy, preeclampsia, and premature rupture of membranes, independent of lactate metabolism. Additionally, adverse pregnancy outcomes can also affect blood mtDNA copy number, suggesting that blood mtDNA copy number may serve as a molecular biomarker for early clinical risk prediction of adverse pregnancy outcomes.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Fibroblast growth factor 1 inhibits podocyte senescence in a mouse model of diabetic nephropathy].","authors":"Huanan Li, Zifan Zhu, Qiaojun Shen, Yihao Wu, Liang Wang, Weigan Shen","doi":"10.3724/zdxbyxb-2025-0414","DOIUrl":"https://doi.org/10.3724/zdxbyxb-2025-0414","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To identify differentially expressed genes (DEGs) associated with diabetic nephropathy and to explore their effects on glomerular podocyte senescence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Renal tissue transcriptome datasets (GSE142025 and GSE199838) were downloaded from the Gene Expression Omnibus (GEO) database, including 39 renal biopsy specimens from patients with diabetic nephropathy and 24 control specimens. The DESeq2 package in R was used for data analysis, with &lt;i&gt;P&lt;/i&gt;&lt;0.05 and |log&lt;sub&gt;2&lt;/sub&gt; fold change| ≥ 1 as the criteria for DEG identification. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the identified DEGs. DEGs involved in senescence-related pathways were further screened and validated in the glomerular transcriptome dataset GSE96804. The expression of these genes was verified using a mouse model of diabetic nephropathy and high glucose-induced podocytes. Subsequently, the effects of fibroblast growth factor 1 (Fgf1) on high glucose-induced podocyte senescence and diabetic nephropathy were analyzed through Fgf1 overexpression and knockdown in mouse podocytes, as well as recombinant Fgf1 (rFgf1) treatment in vivo. RT-qPCR was used to verify DEG expression changes; Masson and PAS staining to detect renal fibrosis and glomerular pathology; Fgf1 and Nephrin immunofluorescence to detect Fgf1 expression in podocytes; SA-β-gal staining to detect podocyte senescence; p16 and Nephrin immunofluorescence to detect senescence-related protein expression; and Western blotting to detect protein expression levels..&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 180 DEGs (89 upregulated, 91 downregulated) were identified in the 39 diabetic nephropathy and 24 control specimens from the GSE142025 and GSE199838 datasets. KEGG analysis showed significant enrichment of these genes in multiple senescence-related signaling pathways, including the MAPK, Rap1, FoxO, and p53 pathways. Validation in the glomerular dataset GSE96804 revealed that FGF1, GADD45B, NR4A1, SRF, and PARD6A were downregulated, while IKBKB was upregulated in the glomeruli of diabetic nephropathy patients, consistent with the previous datasets; the remaining five genes showed no significant changes. In the mouse model, Fgf1 expression was significantly downregulated in renal tissue, while Gadd45b, Nr4a1, Srf, and Ikbkb were upregulated; Pard6a showed no significant difference. In cell models, Fgf1 was downregulated under high glucose, while Ikbkb showed no significant change. Overexpression of Fgf1 in mouse podocytes suppressed the expression of senescence-related genes p21 and p16 and reduced the DNA damage marker γ-H2AX, whereas Fgf1 knockdown had the opposite effect. In vivo, rFgf1 treatment inhibited STZ-induced glomerular extracellular matrix accumulation, reduced glomerular SA-β-gal activity, and lowered the expression of p16, p21, and γ-H2AX in renal tissue and podocytes, thereby ameliorating podocyte senesc","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Huangqin Qingre Chubi Capsules inhibit inflammation and proliferation of fibroblast-like synoviocytes in rheumatoid arthritis via the ALKBH5/circ_0091685/EIF4A3 axis].","authors":"Yuedi Hu, Jian Liu","doi":"10.3724/zdxbyxb-2025-0685","DOIUrl":"10.3724/zdxbyxb-2025-0685","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To clarify the role of the ALKBH5/circ_0091685/EIF4A3 axis in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and to investigate whether a traditional Chinese medicine preparation Huangqin Qingre Chubi Capsules (HQC) regulates inflammation and proliferation of RA-FLS through this axis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Differentially expressed genes (DEGs) between RA patients and healthy controls were screened based on microarray datasets from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify related biological processes and pathways. A co-culture model of peripheral blood mononuclear cells and RA-FLS was established. Through overexpression or silencing of ALKBH5, circ_0091685, and EIF4A3, combined with site-directed mutation of the N&lt;sup&gt;6&lt;/sup&gt;-methyladenosine (m&lt;sup&gt;6&lt;/sup&gt;A) sites within circ_0091685, we verified whether ALKBH5 targets EIF4A3 by mediating m&lt;sup&gt;6&lt;/sup&gt;A modification of circ_0091685, thereby affecting RA-FLS inflammation and proliferation. Meanwhile, an adjuvant-induced arthritis rat model was established to observe the therapeutic effects of HQC &lt;i&gt;in vivo&lt;/i&gt;. Furthermore, HQC containing serum was applied to RA-FLS to explore the underlying mechanism involving the ALKBH5/circ_0091685/EIF4A3 axis. Cell proliferation was assessed by EdU staining; inflammatory cytokine levels were measured by ELISA; mRNA expression of EIF4A3 and circ_0091685 was detected by RT-qPCR; protein expression of ALKBH5 and EIF4A3 was analyzed by Western blotting; the binding between circ_0091685 and EIF4A3 was validated by RNA immunoprecipitation (RIP); total m&lt;sup&gt;6&lt;/sup&gt;A levels and m&lt;sup&gt;6&lt;/sup&gt;A modification on circ_0091685 were detected by colorimetric assay and methylated RNA immunoprecipitation-qPCR, respectively; and histopathological changes in rat knee joints were observed using hematoxylin-eosin, safranin O-fast green, and toluidine blue staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among the top 20 DEGs between RA patients and healthy controls were ALKBH5 and EIF4A3. GO analysis indicated enrichment of methylation-related biological processes, and KEGG analysis identified enriched pathways including the IL-17 signaling pathway. Compared with the ALKBH5 silencing control group, the ALKBH5 silenced group showed decreased expression of ALKBH5/circ_0091685/EIF4A3, reduced levels of IL-6, IL-17A, IL-23, and TNF-α, and a lower proportion of EdU positive cells (all &lt;i&gt;P&lt;/i&gt;&lt;0.01), whereas the ALKBH5 overexpression group exhibited the opposite effects. Compared with the ALKBH5 overexpression+circ_0091685 control group, the ALKBH5 overexpression+circ_0091685 mutant group had significantly reduced IL-6, IL-17A, IL-23, and TNF-α levels (all &lt;i&gt;P&lt;/i&gt;&lt;0.01). RIP assays confirmed that circ_0091685 specifically binds to EIF4A3 protein. Overexpression of circ_0091685 or EIF4A3 increased the levels of IL-6, IL-17A, IL-23, ","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-20"},"PeriodicalIF":0.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Clinical value of cerebrospinal fluid metagenomic next genera-tion sequencing in diagnosing neonatal intracranial infections].","authors":"Lingchen Li, Lizhong DU","doi":"10.3724/zdxbyxb-2025-0965","DOIUrl":"10.3724/zdxbyxb-2025-0965","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the diagnostic performance of cerebrospinal fluid (CSF) metagenomic next generation sequencing (mNGS) for neonatal intracranial infections and its impact on clinical decision making.</p><p><strong>Methods: </strong>A retrospective observational study was conducted. Neonates admitted to the Children's Hospital, Zhejiang University School of Medicine from 2020 to 2025 with suspected intracranial infection who underwent CSF mNGS were enrolled. The sensitivity of mNGS and its concordance with CSF culture and PCR were calculated. Clinical impact was assessed using predefined criteria, and samples were categorized into positive impact and no impact groups to identify independent factors influencing the clinical utility of mNGS.</p><p><strong>Results: </strong>Among 61 neonates with suspected intracranial infection, 48 were confirmed. Pathogens were identified in 18 cases, of which 9 were detected exclusively by mNGS, accounting for 50% of etiological diagnoses. The sensitivity of mNGS was 31.3% (95% CI: 18.7%-46.3%), higher than that of culture PCR (18.8%, 95% CI: 8.9%-32.6%), but the difference was not statistically significant (<i>P</i>=0.15). The positive and negative concordance rates between mNGS and culture PCR were 66.7% (95% CI: 29.9%-92.5%) and 76.9% (95% CI: 60.7%-88.9%), respectively. mNGS positively influenced clinical decisions in 37.7% (23/61) of patients: 12 cases with positive results guided etiological diagnosis and treatment adjustment, and 11 cases with negative results led to antibiotic de escalation or discontinuation. Multivariate analysis identified a positive mNGS result as an independent factor associated with positive clinical impact (OR = 22.127, <i>P</i><0.01).</p><p><strong>Conclusions: </strong>CSF mNGS provides valuable support in etiological diagnosis and clinical decision making for neonatal intracranial infections.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Polydatin attenuates high copper induced damage in Atp7b knockout neural stem cells by regulating PPARG mediated ferroptosis].","authors":"Ni Wang, Kaijian Wu, Wangyun Wei, Wanqing Zhang, FANGMingsheng, Jing Zhang","doi":"10.3724/zdxbyxb-2025-0807","DOIUrl":"https://doi.org/10.3724/zdxbyxb-2025-0807","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the mechanism by which polydatin ameliorates neurological damage in Wilson disease (WD) based on bioinformatics analysis and experimental validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The targets of polydatin were predicted using PharmMapper, SEA, and Swiss Target Prediction databases, while targets related to WD and ferroptosis were retrieved from GeneCards, OMIM, DrugBank, Therapeutic Target Database, and FerrDb. Overlapping targets among polydatin, WD, and ferroptosis were identified. A protein-protein interaction (PPI) network was then constructed using the STRING database and Cytoscape software to screen for core targets. Molecular docking between the core targets and polydatin was performed with AutoDock and visualized using PyMOL. A high copper induced &lt;i&gt;Atp7b&lt;/i&gt; knockout (&lt;i&gt;Atp7b&lt;sup&gt;-/-&lt;/sup&gt;&lt;/i&gt;)neural stem cellmodel was established. Different drug intervention groups and reverse validation groups (including gene transfection) were set up. Cell viability was measured by CCK 8 assay; apoptosis was assessed by flow cytometry and TUNEL staining; mitochondrial membrane potential (MMP) was detected using JC 1 staining; intracellular malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and ferrous iron (Fe&lt;sup&gt;2+&lt;/sup&gt;) levels were determined by colorimetric assays; reactive oxygen species (ROS) levels were measured using the DCFH DA method; mRNA levels of peroxisome proliferator activated receptor gamma (PPARG) and long chain acyl CoA synthetase 4 (ACSL4) were examined by quantitative reverse transcription PCR (qRT PCR); and protein levels of PPARG, ACSL4, nuclear factor erythroid 2 related factor 2 (NRF2), and glutathione peroxidase 4 (GPX4) were analyzed by Western blotting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Network pharmacology analysis identified 443 polydatin targets, 5,772 WD targets, and 564 ferroptosis related targets. Their intersection generated 37 potential therapeutic targets. Topology analysis using CytoNCA identified the top 10 core targets: ALB, PPARG, EGFR, NFE2L2, PTGS2, HMOX1, GSK3B, PARP1, MAPK8, and PPARA. Molecular docking demonstrated a strong binding affinity between polydatin and PPARG, with a binding energy of -9.6 kcal/mol. Compared with the model control group, polydatin treatment significantly enhanced cell viability (&lt;i&gt;P&lt;/i&gt;&lt;0.05) and reduced the apoptosis rate (&lt;i&gt;P&lt;/i&gt;&lt;0.01). The levels of MDA, ROS, and Fe&lt;sup&gt;2+&lt;/sup&gt; were decreased (all &lt;i&gt;P&lt;/i&gt;&lt;0.05), while SOD activity and MMP were significantly increased (all &lt;i&gt;P&lt;/i&gt;&lt;0.01). The protein expression levels of PPARG, NRF2, and GPX4 were significantly upregulated (all &lt;i&gt;P&lt;/i&gt;&lt;0.05), and ACSL4 protein expression was notably downregulated (&lt;i&gt;P&lt;/i&gt;&lt;0.05). Pretreatment with a ferroptosis activator (Erastin), a PPARG antagonist (GW9662), or siPPARG silencing, which inhibit PPARG function or activate ferroptosis, significantly weakened the protective effects of polydatin on cell viability, oxidative str","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[WD40 repeat-containing protein 6 aggravates diabetic kidney disease by promoting lipid accumulation in kidney].","authors":"Peiqing Xin, Lina Sun, Shaona Niu, Xue Sun, Xue Sun","doi":"10.3724/zdxbyxb-2025-0666","DOIUrl":"10.3724/zdxbyxb-2025-0666","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role and mechanism of WD40 repeat-containing protein 6 (WDR6) in the regulation of renal lipid metabolism and its involvement in the progression of diabetic kidney disease (DKD).</p><p><strong>Methods: </strong>A total of 97 patients who underwent renal biopsy in Linyi People's Hospital between 2015 and 2023 were enrolled. Based on pathological diagnoses, the patients were divided into three groups: non-DKD (<i>n</i>=38), DKD stage Ⅱ (<i>n</i>=24), and DKD stage Ⅲ (<i>n</i>=35). Clinical indicators, including complete blood count, liver and kidney function tests, and markers of glucose and lipid metabolism, were assessed. Renal tissue damage was evaluated by renal biopsy pathology. Immunohistochemistry was used to detect the expressions of WDR6 and adipose differentiation-related protein (ADRP). Human renal tubular epithelial (HK-2) cells were stimulated with high glucose, and lipid deposition was observed by oil red O staining. Protein and mRNA levels of lipid metabolism-related molecules were measured by Western blotting and qRT-PCR. Additionally, the effect of small interfering RNA-mediated WDR6 silencing on the above indicators was examined.</p><p><strong>Results: </strong>Compared with the non-DKD group, DKD stage Ⅱ and DKD stage Ⅲ groups exhibited significant abnormalities in renal function- and lipid metabolism-related parameters, along with varying degrees of renal tissue injury. WDR6 was expressed in human kidney, and its expression together with ADRP was elevated in the DKD groups (both <i>P</i><0.01). After 48 hours of high-glucose stimulation, HK-2 cells exhibited prominent lipid deposition, accompanied by increased protein and mRNA levels of WDR6, ADRP, sterol regulatory element-binding protein 1 (SREBP1), and fatty acid synthase compared with the blank control group (all <i>P</i><0.01). Silencing <i>WDR6</i> reduced high glucose-induced lipid deposition and the expression of these lipid metabolism-related molecules (all <i>P</i><0.05).</p><p><strong>Conclusions: </strong>Elevated WDR6 levels may affect renal lipid metabolism, thereby accelerating the pathological progression of DKD.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"465-474"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Progress on prognostic assessment methods for mild cognitive impairment].","authors":"Jingjing Lin, Guran Yu","doi":"10.3724/zdxbyxb-2025-0669","DOIUrl":"10.3724/zdxbyxb-2025-0669","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Mild cognitive impairment (MCI), a key prodromal stage of dementia, requires precise prognostic assessment to delay disease progression. Given the high heterogeneity of MCI, any single indicator has limited predictive efficacy. Different clinical subtypes of MCI, such as amnestic MCI, non-amnestic MCI, and subjective cognitive decline, exhibit fundamental differences in pathological mechanisms and outcomes, forming the basis for stratified prognostic assessment. Abnormal sleep duration, physical functional decline, and psychiatric symptoms (depression, anxiety, apathy) are indicative of cognitive decline risk to varying degrees and can serve as clinical observational indicators for evaluating MCI prognosis. Neuropsychological assessment scales and instrumental activities of daily living assessments can characterize the features of cognitive impairment, but their results are susceptible to educational and cultural influences. Core cerebrospinal fluid (CSF) biomarkers, including amyloid β-protein (Aβ)&lt;sub&gt;42&lt;/sub&gt;, phosphorylated tau protein (P-tau)181, and total tau protein (T-tau), are highly correlated with the core pathology of Alzheimer's disease and can accurately predict MCI prognosis. Plasma biomarkers such as P-tau217, neurofilament light chain, glial fibrillary acidic protein (GFAP), and the Aβ&lt;sub&gt;42&lt;/sub&gt;/Aβ&lt;sub&gt;40&lt;/sub&gt; ratio are suitable for screening and follow-up; combining CSF and plasma biomarkers enhances predictive performance. In contrast, serum markers like Klotho and insulin-like growth factor-1 lack specificity, and their independent predictive value requires further validation. Multimodal neuroimaging, including structural magnetic resonance imaging (MRI), functional MRI (revealing neural network compensation and decompensation), and positron emission tomography (PET) showing molecular pathological changes (Aβ deposition, tau protein aggregation), can form a complete chain of evidence linking molecular events to clinical phenotypes. Intelligent prediction models, ranging from basic risk stratification and static integrated models to longitudinal dynamic prediction, significantly improve the fusion predictive performance of multimodal data. Consequently, the prognostic assessment of MCI is moving from a single modality toward a stepwise integrated approach: primary screening adopts the combination of clinical information (including MCI subtype characteristics)+core neuropsychological assessment (focusing on delayed recall and executive function subtests of the Montreal Cognitive Assessment)+blood biomarkers (plasma P-tau217 and GFAP testing); the precise diagnostic phase adds structural MRI to assess hippocampal atrophy; for difficult cases and research settings, CSF testing, Aβ-PET, and τ-PET are further introduced. Future research should focus on constructing dynamic monitoring frameworks and deepening mechanistic exploration of modifiable risk factors, thereby advancing individualized prognostic management and early","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"449-464"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Quercetin, a key bioactive component of Zuogui Pill, protects against Alzheimer<b>'</b>s disease by regulating the PI3K/Akt signaling pathway].","authors":"Guangya Li, Peize Li, Liuling Huang, Jingwen Zhu, Xiude Qin, Yunwei Lu","doi":"10.3724/zdxbyxb-2025-0661","DOIUrl":"10.3724/zdxbyxb-2025-0661","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;To investigate the protective mechanism of quercetin, a key bioactive component of Chinese medicine Zuogui Pill, against Alzheimer's disease (AD) via the PI3K/Akt signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The TCMSP, PubChem, SwissTargetPrediction, and BATMAN-TCM databases were used to retrieve the active components of Zuogui Pill and predict their potential targets. Target information was standardized using the UniProt database. AD-related target genes were obtained from DrugBank, GeneCards, and OMIM, and the intersection was taken to identify the potential targets of Zuogui Pill for AD treatment. Based on these targets, a protein-protein interaction network was constructed using Cytoscape 3.10.1 and the STRING database. The key active components and core targets of Zuogui Pill for AD treatment were identified through computational analysis. Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the potential targets to explore the biological processes and signaling pathways involved. Subsequently, molecular docking and binding affinity prediction between the key active component quercetin and the core target Akt1 were performed using the online tool CB-Dock2. An AD cell model was established by treating mouse hippocampal neuron cells (HT22) with amyloid β-protein&lt;sub&gt;1-42&lt;/sub&gt; (Aβ&lt;sub&gt;1-42&lt;/sub&gt;) oligomers. The cells were divided into low-, medium-, and high- dose quercetin groups, and a PI3K agonist (EGF) group for &lt;i&gt;in vitro&lt;/i&gt; experiments. To verify whether quercetin exerts its anti-apoptotic effects by regulating the PI3K/Akt pathway, additional groups were established: PI3K inhibitor (LY294002) group, PI3K inhibitor+high-dose quercetin group, and PI3K inhibitor+EGF group. CCK-8 assay was used to detect cell viability; JC-1, Calcein-AM/PI, and Hoechst staining were used to assess apoptosis; and Western blotting was used to detect expression of PI3K/Akt signaling pathway and apoptosis related proteins.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Network pharmacology demonstrated that quercetin targets core proteins such as Akt1 in a network manner and is predominantly enriched in the PI3K/Akt signaling pathway. Molecular docking showed favorable binding affinity between quercetin and Akt1 (binding energy: －6.6 kcal/mol). In the Aβ&lt;sub&gt;1-42&lt;/sub&gt; oligomer-induced HT22 neuronal cell model and HT22 cells treated by PI3K inhibitor, high-dose quercetin significantly increased cell viability, elevated the p-Akt/Akt ratio and Bcl-2 expression level (all &lt;i&gt;P&lt;/i&gt;&lt;0.05), reduced the cleaved caspase-3/caspase-3 ratio as well as the expression levels of BAX and cytochrome C (all &lt;i&gt;P&lt;/i&gt;&lt;0.01), and alleviated apoptosis of HT22 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Quercetin, a key bioactive component of Chinese medicine Zuogui Pill, inhibits neuronal apoptosis by regulating the PI3K/Akt signaling pathway, thereby exerting a protective eff","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"414-424"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145709110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Bushen Yijing Formula attenuates amyloid β-protein deposi-tion and oxidative damage in <i>Caenorhabditis elegans</i>].","authors":"Yunwei Lu, Deyu Li, Yingchao Hu, Lei Lu, Guran Yu","doi":"10.3724/zdxbyxb-2025-0419","DOIUrl":"10.3724/zdxbyxb-2025-0419","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the protective effects of Chinese medicine Bushen Yijing Formula against amyloid β-protein (Aβ) deposition and oxidative damage using models of <i>Caenorhabditis elegans</i>.</p><p><strong>Methods: </strong>The <i>C. elegans</i> models, including wide-type strains N2, transgenic strains CL4176, TJ356, and LG333, were employed. The herbal components of the formula were water‑extracted, freeze‑dried into lyophilized powder, and added to the culture medium at different concentrations. Oxidative stress was induced by paraquat exposure. Evaluated parameters included lifespan; time to paralysis and pharyngeal Aβ deposition in CL4176; levels of total antioxidant capacity, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) measured by commercial kits; apoptosis detected by acridine orange staining; nuclear translocation of DAF‑16::GFP in TJ356 nematodes and SKN-1::GFP in LG333 nematodes observed under fluorescence microscopy. Molecular docking and dynamics simulations were further performed to assess the binding stability of the active components catalpol and tetrahydroalstonine (THA) with the core targets FOXO and Nrf2.</p><p><strong>Results: </strong>Compared with the normal control group, Bushen Yijing Formula significantly extended the lifespan of N2 nematodes under both oxidative stress and normal conditions (all <i>P</i><0.01). Compared with the control group of the AD model, Bushen Yijing Formula prolonged the time to paralysis and reduced pharyngeal Aβ deposition in CL4176 (all <i>P</i><0.01). Compared with the control group in the paraquat-induced oxidative stress model in N2, Bushen Yijing Formula elevated total antioxidant capacity, SOD, CAT, and GSH levels (all <i>P</i><0.01), decreased MDA and ROS levels (all <i>P</i><0.05), and attenuated apoptosis. Moreover, the formula promoted nuclear translocation of DAF‑16 and SKN‑1 (all <i>P</i><0.01). Molecular docking revealed that binding energies of catalpol and THA with FOXO and Nrf2 were all below －7.00 kcal/mol, and dynamics simulations confirmed high stability and favorable affinity for the FOXO-catalpol, Nrf2-catalpol, and Nrf2-THA complexes.</p><p><strong>Conclusions: </strong>Bushen Yijing Formula alleviates Aβ deposition and its neurotoxicity, enhances antioxidant capacity, and attenuates oxidative stress injury in model nematodes, likely through stable binding and regulation of the FOXO/Nrf2 signaling pathway.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"425-436"},"PeriodicalIF":0.0,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13439443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}